Premium
Linear double‐stranded DNA s as innovative biological parts to implement genetic circuits in mammalian cells
Author(s) -
Li Shuai,
Su Weijun,
Zhang Chunze
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14816
Subject(s) - dna , double stranded , biology , genetics
Synthetic biology employs engineering principles to redesign biological systems for biomedical or industrial purposes. Innovation and application of original biological parts for genetic circuit construction will significantly facilitate and expedite the development of synthetic biology. Here, we built two‐ or three‐input linear double‐stranded DNA (lds DNA )‐based Boolean AND gate genetic circuits in mammalian cells. Bioluminescence imaging revealed the feasibility of lds DNA ‐based Boolean AND gate circuits in vivo . Inhibition of DNA ‐ PK cs, a pivotal enzyme in nonhomologous end joining, significantly attenuated the output signals from lds DNA ‐based Boolean AND gate circuits. We further showed that lds DNA with additional terminal random nucleotide(s) could undergo end nucleotide deletion and generate in‐frame proteins via the Boolean AND gate response. Additionally, lds DNA s or plasmids with identical overlapping sequences could also serve as input signals for Boolean AND gate genetic circuits. Our work establishes lds DNA s as innovative biological parts for building low noise‐signal ratio Boolean AND gate circuits with application potential in biomedical engineering fields.